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Familial liability in the functional psychoses had traditionally been examined by comparing mutually exclusive diagnostic categories. This study examines overlapping psychopathological dimensions in relation to familial morbid risk of psychosis.
We tested for associations between seven factor-analysis derived psychopathological dimensions and familial morbid risk of psychosis, in a sample of 150 patients with recent-onset functional psychosis and 548 of their first-degree relatives.
A syndrome characterised by affective blunting and insidious and early onset of illness, non-specifically predicted psychosis in the first-degree relatives, whereas a manic syndrome specifically predicted affective psychosis in the relatives. No other main effects were observed, but there were interactions with proband diagnosis: a syndrome characterised by bizarre behaviour, inappropriate affect, catatonia and poor rapport predicted psychosis in relatives of schizophrenic probands, and a syndrome of depressive: symptoms predicted psychosis in relatives of schizoaffective probands. Positive symptoms were not associated with illness in the relatives.
Genetic effects in the functional psychoses may comprise non-specific components that canalise a general, early-onset, affective blunting phenotype and several other, more specific, influences on phenotypic variation.
It has been suggested that in schizophrenia an association exists between family history of schizophrenia and poor outcome on the one hand, and family history of affective disorders and good outcome on the other.
We tested for associations between four-year outcome and familial loading for psychotic disorders in a mixed sample of 150 consecutively admitted patients with functional psychosis (schizophrenia, psychotic affective disorders, other psychotic disorders) of recent onset. For each proband, a familial loading score for (i) broadly defined psychotic disorder, (ii) schizophrenia, and (iii) affective disorder was calculated using information on relatives obtained through the Family History Research Diagnostic Criteria method and direct interviews of relatives with the Schedule for Affective Disorders and Schizophrenia.
In our sample of psychotic patients, familial loading for psychotic disorder predicted persistent negative symptoms over the follow-up period (OR 1.5; 95% CI 1–2.2), especially in schizophrenia, and was also associated with more time hospitalised (P > 0.05), and more social disability at follow-up (P < 0.05). Greater familial loading for schizophrenia predicted a greater likelihood of non-recovery (OR 2.2; 95% CI 1.1–4.4) and a greater likelihood to have had persistent negative symptoms over the follow-up period (OR 1.7; 95% CI 0.9–3.1). No association was found between outcome and familial loading for affective disorder.
We conclude that familial loading may be a continuous risk factor for some dimensions of clinical outcome in the functional psychoses. This suggests that there is a continuum of genetic liability not only to the emergence of psychotic illness, but also the subsequent chronicity of the disorder.
Although a genetic component in schizophrenia is well established, it is likely that the contribution of genetic factors is not constant for all cases. Several recent studies have found that the relatives of female or early onset schizophrenic patients have an increased risk of schizophrenia, compared to relatives of male or late onset cases. These hypotheses are tested in the current study.
A family study design was employed; the probands were 195 patients with functional psychosis admitted to three south London hospitals, diagnosed using Research Diagnostic Criteria (RDC), and assessed using the Present State Examination (PSE). Information on their relatives was obtained by personal interview of the mother of the proband, and from medical records. Psychiatric diagnoses were made using Family History – Research Diagnostic Criteria (FH-RDC), blind to proband information.
There was a tendency for homotypia in the form of psychosis within families. The lifetime risk of schizophrenia in the first degree relatives of schizophrenic probands, and the risk of bipolar disorder in the first degree relatives of bipolar probands, were 5–10 times higher than reported population risks. Relatives of female and early onset (<22 years) schizophrenic probands had higher risk of schizophrenia than relatives of male and late onset schizophrenic probands. However, this effect was compensated in part by an excess of non-schizophrenic psychoses in the relatives of male probands.
These results suggest a high familial, possibly genetic, loading in female and early onset schizophrenia, but do not resolve the question of heterogeneity within schizophrenia.
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